Discovery of 8-hydroxyadenines as a novel type of interferon inducer

被引：75

作者：

Hirota, K ^{[1
]}

Kazaoka, K

Niimoto, I

Kumihara, H

Sajiki, H

Isobe, Y

Takaku, H

Tobe, M

Ogita, H

Ogino, T

Ichii, S

Kurimoto, A

Kawakami, H

机构：

[1] Gifu Pharmaceut Univ, Med Chem Lab, Gifu 5028585, Japan

[2] Japan Energy Corp, Pharmaceut & Biotechnol Lab, Toda, Saitama 3350026, Japan

[3] Sumitomo Pharmaceut, Div Res, Konohana Ku, Osaka 5540022, Japan

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2002年 / 45卷 / 25期

关键词：

D O I：

10.1021/jm0203581

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

9-Benzyl-8-hydroxyadenine (6) was found to possess interferon-inducing activity in vitro as a lead compound. Although replacement of the 9-benzyl group of 6 did not improve the activity, the introduction of a substituent such as alkyl, alkylthio, alkylamino, and alkoxy groups into the 2-position of the adenine ring resulted in a remarkable increase in the activity. The 2-alkylthio (30-32), 2-butylamino (41), and 2-butoxy (47) analogues indicated the highest activities by oral administration to mice.

引用

页码：5419 / 5422

页数：4

共 26 条

[1] ACYLATION OF NITROGEN HETEROCYCLES .2. CARBOBENZOXYLATION OF SUBSTITUTED ADENINES UNDER CONDITIONS OF SCHOTTEN-BAUMANN REACTION [J].

ALTMAN, J ;

BENISHAI, D .

JOURNAL OF HETEROCYCLIC CHEMISTRY, 1968, 5 (05) :679-&

[2] Imiquimod and resiquimod as novel immunomodulators [J].

Dockrell, DH ;

Kinghorn, GR .

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2001, 48 (06) :751-755

[3] PURINES .13. RING-OPENING OF 3-ALKYLADENINES WITH CARBOBENZOXY CHLORIDE - TRANSFORMATION INTO 8-HYDROXYLATED ADENINES [J].

FUJII, T ;

SAITO, T .

CHEMICAL & PHARMACEUTICAL BULLETIN, 1973, 21 (09) :1954-1959

[4] ANTIVIRAL ACTIVITY AND INDUCTION OF INTERFERON-LIKE SUBSTANCE BY QUINACRINE AND ACRANIL [J].

GLAZ, ET ;

SZOLGAY, E ;

STOGER, I ;

TALAS, M .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1973, 3 (05) :537-541

[5] Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway [J].

Hemmi, H ;

Kaisho, T ;

Takeuchi, O ;

Sato, S ;

Sanjo, H ;

Hoshino, K ;

Horiuchi, T ;

Tomizawa, H ;

Takeda, K ;

Akira, S .

NATURE IMMUNOLOGY, 2002, 3 (02) :196-200

[6] CONVENIENT METHOD FOR THE SYNTHESIS OF C-ALKYLATED PURINE NUCLEOSIDES - PALLADIUM-CATALYZED CROSS-COUPLING REACTION OF HALOGENOPURINE NUCLEOSIDES WITH TRIALKYLALUMINUMS [J].

HIROTA, K ;

KITADE, Y ;

KANBE, Y ;

MAKI, Y .

JOURNAL OF ORGANIC CHEMISTRY, 1992, 57 (19) :5268-5270

[7] Novel and efficient synthesis of 8-oxoadenine derivatives [J].

Hirota, K ;

Kazaoka, K ;

Niimoto, I ;

Sajiki, H .

HETEROCYCLES, 2001, 55 (12) :2279-2282

[8] N,N-DIOCTADECYL-N',N'-BIS(2-HYDROXYETHYL) PROPANEDIAMINE - ANTIVIRAL ACTIVITY AND INTERFERON STIMULATION IN MICE [J].

HOFFMAN, WW ;

KORST, JJ ;

NIBLACK, JF ;

CRONIN, TH .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1973, 3 (04) :498-502

[9] PURINE NUCLEOSIDES .7. DIRECT BROMINATION OF ADENOSINE DEOXYADENOSINE GUANOSINE + RELATED PURINE NUCLEOSIDES [J].

HOLMES, RE ;

ROBINS, RK .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1964, 86 (06) :1242-&

[10] SYNTHESIS OF SOME IODOPURINE DERIVATIVES [J].

KODA, RT ;

BILES, JA ;

WOLF, W .

JOURNAL OF PHARMACEUTICAL SCIENCES, 1968, 57 (12) :2056-&

← 1 2 3 →